Neurocritical Care

, Volume 24, Issue 1, pp 6–46 | Cite as

Guideline for Reversal of Antithrombotics in Intracranial Hemorrhage

A Statement for Healthcare Professionals from the Neurocritical Care Society and Society of Critical Care Medicine
  • Jennifer A. FronteraEmail author
  • John J. Lewin III
  • Alejandro A. Rabinstein
  • Imo P. Aisiku
  • Anne W. Alexandrov
  • Aaron M. Cook
  • Gregory J. del Zoppo
  • Monisha A. Kumar
  • Ellinor I. B. Peerschke
  • Michael F. Stiefel
  • Jeanne S Teitelbaum
  • Katja E. Wartenberg
  • Cindy L. Zerfoss
Review Article



The use of antithrombotic agents, including anticoagulants, antiplatelet agents, and thrombolytics has increased over the last decade and is expected to continue to rise. Although antithrombotic-associated intracranial hemorrhage can be devastating, rapid reversal of coagulopathy may help limit hematoma expansion and improve outcomes.


The Neurocritical Care Society, in conjunction with the Society of Critical Care Medicine, organized an international, multi-institutional committee with expertise in neurocritical care, neurology, neurosurgery, stroke, hematology, hemato-pathology, emergency medicine, pharmacy, nursing, and guideline development to evaluate the literature and develop an evidence-based practice guideline. Formalized literature searches were conducted, and studies meeting the criteria established by the committee were evaluated.


Utilizing the GRADE methodology, the committee developed recommendations for reversal of vitamin K antagonists, direct factor Xa antagonists, direct thrombin inhibitors, unfractionated heparin, low-molecular weight heparin, heparinoids, pentasaccharides, thrombolytics, and antiplatelet agents in the setting of intracranial hemorrhage.


This guideline provides timely, evidence-based reversal strategies to assist practitioners in the care of patients with antithrombotic-associated intracranial hemorrhage.


Anticoagulant Antiplatelet Antithrombotic Intracranial hemorrhage Intracerebral hemorrhage Intraparenchymal hemorrhage ICH Subarachnoid hemorrhage SAH Subdural hematoma SDH Reversal Antidote Vitamin K antagonist VKA Warfarin Coumadin Direct thrombin inhibitor DTI Dabigatran Factor Xa inhibitor Apixaban Rivaroxaban Edoxaban Low-molecular weight heparin Heparin Heparinoid Pentasaccharide Fondaparinux TPA rtPA Alteplase Thrombolytic Plasminogen activator Aspirin Clopidogrel Prothrombin complex concentrates PCC aPCC FEIBA Activated prothrombin complex concentrates FFP Fresh frozen plasma Recombinant factor VIIa rFVIIa Protamine Platelets DDAVP Desmopressin Cryoprecipitate Guideline GRADE criteria 



We would like to thank Zoe Oliver, MD and Frederick A. Zeiler, MD for their contributions to this document.

Compliance with Ethical Standards


D. Aisiku serves on the National Advisory Board for the Medicines Company, Dr. Alexandrov serves on the speakers bureau for Genentech. Dr. del Zoppo has received research funds from the NIH, Boehringer Ingelheim, and Novartis. He has served on advisory boards for Boehringer Ingelheim, Daiichi-Sankyo, and Novartis. Dr. Kumar has received support from Haemonetics. Dr. Stiefel serves as a consultant for Medtronic and Penumbra. The remaining authors have nothing to disclose.

Supplementary material

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Supplementary material 1 (DOCX 103 kb)
12028_2015_222_MOESM2_ESM.docx (37 kb)
Supplementary material 2 (DOCX 37 kb)
12028_2015_222_MOESM3_ESM.docx (71 kb)
Supplementary material 3 (DOCX 71 kb)


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Jennifer A. Frontera
    • 1
    Email author
  • John J. Lewin III
    • 2
  • Alejandro A. Rabinstein
    • 3
  • Imo P. Aisiku
    • 4
  • Anne W. Alexandrov
    • 5
    • 6
  • Aaron M. Cook
    • 7
  • Gregory J. del Zoppo
    • 8
  • Monisha A. Kumar
    • 9
  • Ellinor I. B. Peerschke
    • 10
  • Michael F. Stiefel
    • 11
  • Jeanne S Teitelbaum
    • 12
  • Katja E. Wartenberg
    • 13
  • Cindy L. Zerfoss
    • 14
  1. 1.The Cerebrovascular Center, Neurological InstituteCleveland Clinic and Case Western Reserve UniversityClevelandUSA
  2. 2.The Departments of Pharmacy and Anesthesiology & Critical Care MedicineThe Johns Hopkins Hospital and Johns Hopkins University School of MedicineBaltimoreUSA
  3. 3.The Department of NeurologyMayo ClinicRochesterUSA
  4. 4.Harvard Medical SchoolBrigham and Women’s HospitalBostonUSA
  5. 5.The University of Tennessee Health Science CenterMemphisUSA
  6. 6.Australian Catholic UniversitySydneyAustralia
  7. 7.Department of Pharmacy (UK Healthcare) & Department of Pharmacy Practice & Science (UK College of Pharmacy)University of KentuckyLexingtonUSA
  8. 8.The Departments of Medicine (Hematology) and NeurologyUniversity of Washington School of MedicineSeattleUSA
  9. 9.The Departments of Neurology, Neurosurgery, Anesthesiology & Critical Care, Perelman School of MedicineHospital of the University of PennsylvaniaPhiladelphiaUSA
  10. 10.The Department of Laboratory Medicine and PathologyMemorial Sloan Kettering Cancer Center and Weill Cornell Medical SchoolNew YorkUSA
  11. 11.The Department of Neurosurgery, Westchester Medical CenterNew York Medical CollegeValhallaUSA
  12. 12.Hôpital du Sacré-Coeur and University of Montreal and Montreal Neurological Institute and McGill UniversityMontrealCanada
  13. 13.Klinik für Neurologie, Martin-Luther-Universität Halle-WittenbergHalleGermany
  14. 14.The Neuroscience and Neurosurgery DepartmentsCentra Lynchburg General HospitalLynchburgUSA

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